Submitted on September 17, 2008
Revised on December 1, 2008
Accepted on December 30, 2008
20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model
Pablo Kizelsztein1*, Dmitry Govorko1, Slavko Komarnytsky1, Alysa Evans1, Zhong Wang2, William T Cefalu2, and Ilya Raskin1
1 Rutgers University
2 Pennington Biomedical Research Center
* To whom correspondence should be addressed. E-mail: pablok{at}aesop.rutgers.edu.
The steroid hormone 20-hydroxyecdysone (20HE) is an essential signaling molecule that modulates molting response in insects and may function as a putative anabolic factor in vertebrate animals, although no mammalian 20HE receptor has been identified. Here we show that in H4IIE cell culture, 20HE treatment decreased expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), reduced glucose production, and induced Akt2 phosphorylation sensitive to the phosphoinositide-3 kinase (PI-3K) pathway specific inhibitor LY-294002. Daily oral administration of 20HE (10 mg/kg for 13 weeks) ameliorated obesity and insulin resistance in C57BL/6J mice fed a high-fat diet and produced a significant decrease of body weight gain and body fat mass compared to non-treated animals as demonstrated by dual-energy x-ray absorptiometry analysis. In addition, plasma insulin levels and glucose tolerance were significantly lowered by 20HE treatment. These changes were accompanied by the reduced hepatic expression of PEPCK and G6Pase and increased adiponectin production by visceral fat tissue. These studies demonstrate the anti-obesity and anti-diabetic effects of 20HE and begin to elucidate its putative cellular targets both in vitro and in vivo.
